NYMC Faculty Publications
Journal Title
Advances in Enzymology and Related Areas of Molecular Biology
First Page
307
Last Page
360
Document Type
Article
Publication Date
2-2011
Department
Biochemistry and Molecular Biology
Abstract
Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental effects of paracatalytic reactions may be greatly increased by cellular compartmentation of enzymes and intermediates. For example, in two of the the three multienzyme complexes involved in oxidative α-keto acid decarboxylation, paracatalytic reactions of the third component inactivate the first carbanion-generating component.
In this review we provide an outline of carbanion-generating enzymes known to catalyze paracatalytic reactions. We also discuss the potential of some of these reactions to contribute to irreversible damage in cancer and neurodegeneration through disease-induced alterations in the metabolic state and/or protein structure.
Recommended Citation
Bunik, V., Schloss, J., Pinto, J. T., Dudareva, N., & Cooper, A. J. (2011). A Survey of Oxidative Paracatalytic Reactions Catalyzed by Enzymes That Generate Carbanionic Intermediates: Implications for ROS Production, Cancer Etiology, and Neurodegenerative Diseases. Advances in Enzymology and Related Areas of Molecular Biology, 77, 307-360. https://doi.org/10.1002/9780470920541.ch7
Publisher's Statement
This is the peer reviewed version of the following article: Bunik VI, Schloss JV, Pinto JT, Dudareva N, Cooper AJL (2011) A survey of oxidative paracatalytic reactions catalyzed by enzymes that generate carbanionic intermediates: Implications for ROS production, cancer etiology, and neurodegenerative diseases. Adv Enzymol Relat Areas Mol Biol 77:307–360, which has been published in final form at https://doi.org/10.1002/9780470920541.ch7. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
